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MICR 2420 > Introduction to the innate immune system > Flashcards

Introduction to the innate immune system Flashcards

1
Q

if we are surrounded by microbes why are we not sick more foten

A

not all are disease causing (pathogens)

  • have first line of defense = innate immune system with chemical and physical barriers

chem = antimicrobial peptides, ph of stomach while physical is like the skin

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2
Q

what is the immune system composed of? what are the roles?

A
  • immune system = complex and interconnected system of lyphoid organs, tissues, cells and cell soluble products
  • roles include: recognizing, neutralizing, and/or eliminating potential pathogenic organisms and substrates
  • collectively immune system can respond to nearly all foreign/non self molecular stuctures
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3
Q

what are the 2 arms to the mammalian immune system

A

Innate

  • first like of defense - barriers to infection
  • non specific responses to destroy invaders
  • present at birth - kicks in immediately
  • does not retain memory - no amplidication and non adaptive

Adaptive

  • reaction to specific antigens - parts of proteins, sugars etc
  • body reacts to antigens when exposed- requires innate
  • retains a memory of those antigens - faster response the second time
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4
Q

what are the 3 compoents to the innate immune system

A

*also called non-specific or non adpative immune system

  • 3 components are:
    1. physical barriers that prevent entry
    2. chemical and cellualr barriers which become involved when the physical barriers are breached
    3. Normal microbiota
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5
Q

why does infection not necessarily result in disease? what does the pathogen need to cause disease?

A

*if the immune system is effective and/or the number of infecting organisms is small then noramlly disease will not follow infection

  • to get disease pathogen needs to have:
    1. breach the host physical adn chemicacl barriers
    2. survive the innate defenses (like macrophages), attaach, colonize *exploit host resources and begin to multiple
    2. surmount the last line of defense - adaptive immunity
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6
Q

describe the physical barriers of the innate immune system

A
  • located at the body to external environemnt interface
  • barrier features include: tight junctions between cells, cells are continuously shed and replaced, normal microbiota, chemical barriers and cellular barriers
    ex: simple squamous epithelium, simple cuboidal epithelium, columnar epitheliam, stratified squamous epithelium
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7
Q

describe the skin as a barrier

A
  • epidermis is dry, thick and impenetrable - protects the epidermis
  • dead cells continually shed
  • antimicrobial secretions (ketain, oil glands (sebum), salt (sweat), acidic pH, lysozyme etc)
  • dermis and hypodermid have phagocytic langerhans cells to kill invaders

*even if top layer of skin is breached have more layers to rpotect

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8
Q

describe the mucosal barriers

A
  • layer os epithelial cells connected to each other by tight junctions
  • goblet cells secrete mucus which traps invaders and particulate matter

*thick mucus layer/barrier: protects epithalial cells, bacteria, particles

  • mucosal cells are continually sloughed off -removed
  • respiratory system epithelial cells have ciliary processes which work with mucus to create mucociliary escalator *moves/sweeps mucus and microbes up and out to be attacked by innate immune
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9
Q

describe the GI tract as a barrier

A
  • continuous sloughing off and replacement of mucosal epithelial layers
  • organ specific environemnts (ph, digestive enzymes, bile salts, aerobic to anaerobic, peristalsis and emptying of contents)
  • the GI system possesses an innate system called Gut associated lymphoid tissue (GLAT)
  • specialized M-cells take up microbes form the intestine and release them on the other side for uptake by macrophages

* essentail step in the activation of adaptive immune reposne

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10
Q

describe the mechanicl defenses

A
  • eliminate reduce and inactivate microbes
  • tears & blinking, tight junctions
  • mucus & mucociliary escalator
  • intestinal peristalsis &defication
  • urine flushing helps to maintain a sterile environement in the upper urinary tract
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11
Q

developemnt of microbiota

A

* bodies carry about 10x as many microbial cells as mucleated human cells

  • the consortium of colonizing microbes is doubbed the human microbiota or microbiome
  • recent evidence suggests that the microbiome develops beore birth - outside of the embryonic sac babies are exposed to microbiome of the birth canal and outside worls
  • young babies actually have more diverse microbiome than adults
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12
Q

describe the microbiota of the skin

A
  • skin is diffulct to colonize bc dry, salty, protective oils & enzymes
  • 10^12 microbes in moist areas - scalp, ears, armpits, genetal and anal areas
  • mostly fram positive bacteria - more resistant to salt, acidity and dryness
    ex: staphylococcus epidermidis and cutibacterium acnes
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13
Q

describe the microbiota of the Genitourinary tract

A
  • much of the genitourinary tract is normally free from microbes - urine is sterile
  • the urethra contains staphylococcus epidermidis and some members of enterobacteriaceae (may cause UTI)
  • composition of the vaginal microbiota changes with the menstrual cycle

*acidic secretions favour lactobacillus crispatus

  • antibacterial antibiotic therapy allows Candida albians to proliferate causing a yeast infection
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14
Q

describe the microbiota of the GI tract

A
  • stomach is very acidic pH 1-3 so few can survie
    ex: Helicobacter pylori (causes gastic ulcers and gastric cancer which survives by burrowing intot he thick rpotective mucus barrier - muscus barrier protects endothelial cells
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15
Q

decreased stomach acidity is called ____ and allows ___ to survive

A
  • called hypochlorydia
  • caused by malnourishment
  • decreased acidity allows vibrio cholerae to survive stomach passage
  • establishes infection in less acidic intestine
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16
Q

decribe the microbiota of intestines

A

contain 10^11 - 10^13 bacteria/gm of feces

  • 1000 anaerobes: 1 faculative organism
  • low oxygen environemnt - small amount of oxygen that diffuses fromt he intestinal wall into the lumen is immediately consumed by facultative bacteria like E.coli
  • bacterial species and a few methanogenic archaea comprise the intestinal microbiome
17
Q

what are the benefits and risks of microbiota

A
  • bacteria do not possess hostile intent, only need to find food
  • commensal microbes benefit the human host - make vitamins and digest food (breakdown complex carbohydrates itno products that can be abs), prevent colinzation by pathogens and promote host tissue development
    ex: akkermansia municiphila promotes host tissue differentiation by degredatoin of the mucin layer
  • gut microbiome is maintained by secreting complex carbohydrates (mucins) and hormones

*everything works as longa s it stays wehre it belongs

18
Q

what can alter the gut microbiome

A
  • emotional stress, change in diet, or antibiotic therapy
  • resultant dysbiosis can lead to poor digestion or inflammatory bowel disease (IBD)
19
Q

what causes sporotrichosis/rose gardeners disease

A

-sporothrix shenkii - an opportunistic fungi found in soils

20
Q

what are opportunistic pathogens

A
  • microbes that do not cause infections or disease in immunocompetent hosts
21
Q

what are the two things that rpoduce chemical mediators

where can you fidn them

A

the body (endogenous) or microbiomes (exogenous)

  • plasma and body fluids (sweat sebum, slaiva, tears, breast milk and GI tract secretions) contain a large number of chemcial mediators with antimicrobial properties
22
Q

what do chemcial barriers/ mediators do

A
  • broadly active aginst most/ wide range of microbes
  • destory cell membranes, digest cell walls, inhibit growth and may enhance killing by the body’s cellular defenses
23
Q

types of chemical barriers and mediators

A
  • antimicrobial peptides

acute phase proteins

cytokines - chemical language of/between cells

  • complement proteins
  • inflammation adn fever
24
Q

what are the antimicrobial properties of chemical mediators

A
  • acidic pH, salt, low O2
  • lysozymes, pancreatic enzymes
  • bile salts and lung sufactants
  • lactoferrins and transferrins bind and sequester iron
  • microbiota produce antimicrobial products
25
Q

what are antimicrobial peptides

A
  • small 9-30 aa, mostly cationic peptides
  • found in all life forms - distrupt membranes, enter cells and disrupt cellular functions
  • rpoducts by a variety of human cells
  • secreted or stored in cytoplasmic granules until relseased
  • able to lyse most microbial cells and some enveloped peptides - can be broadly active or specific to a group
    ex: defensine (fungi bacteria, enveloped viruses), source = epithelial cells, macrophages, neutrophils, paneth cells of small intestines
    ex: Histatins (fungi): source = saliva
26
Q

what are acute phase proteins

A
  • produced by the liver and are present in the plasma
  • potentiate and enhance recognizing and kiling of invaders (by phagocytes)
  • antimicrobial properties

*help with recognizing so innat eimmune can racognize and phagocytoze

27
Q

what are cytokines

A
  • include interlukins, chemokines, interferons
  • proteins that are produced by a wide variety of body in response to a signal - epethialial cells, cells of the inante and adaptive immune repsonses
  • chemical language by which cells communicate - autocrine, paracrine and endocrine

*cytokines can be localized to one cell that secretes and receives (autocrine), secreted to nearby cell (paracrine), secreted to circulatory system (endocrine)

* can communicate that there is a problem like a pathogen

28
Q

what do cytokines do to communicate

A
  • bind to cytokine receptors on target cells and induce a specific response
  • can be sitmulatory or inhibitory - differentiation, proliferation, secretion of other cytokines, apoptosis, chemotaxis, phagocytosis ect
    note: know what differentaion, proliferation is
29
Q

what is the complement system

A
  • chemical mediator
  • consists of about 30 proteins mostly made in the liver - then enter blood nd circulate into tissues all over the bdoy
  • named complement bc work with antibodies to enhance killing of pathogensb
  • -* proteins circulate in inactive forms
  • several are proteases - they activate eachother via proteolytic cleavage generatinga complement cascade
  • include soluble and membrane bound proteins and protens with inhibitory/regulatoy functions
30
Q

what are the 3 routes to complement activation

A
  • calssical pathway - assocaited with antigen and antibodies (part of adaptive immunity)
  • alternative pathway- assocaited with innate immune system

*alternative is the only one directly associated with innate

-lectin pathway- requires synthesis of mannose binding lectuin by the liver in response to macrophage cytokines

*dectects carbohydrates and polysaccarides on surface of pathogens

31
Q

complement pathway

A
32
Q

describe the alternative complement pathway

A

** begins with complement factor C3

  1. C3 spontaneously cleaves slowly into C3A and C3B
  2. if C3B meets LPS on invading gram neg microbe, C3B becomes stable and binds to factor B
  3. factor B susceptible to cleavage by another protein -factor D
  4. resulting complex called C3bBb is changed into C5 convertase by properdin (another serum protein)
  5. C5 convertase cleaves C5 in serum into C5a and C5b
  6. C5b now starts to form a prepore complex by binding to C6 and C7
  7. resulting C5bC6C7 complex binds to membranes. C8 and C9 facors join to form the membrane attack complex (MAC) becoming a destructinve pore in the membrane of the target cell
33
Q

describe the MAC complex

A
  • complement C5b protein binds C6 and C7

*C5 comes in and sits on membrane - recurits C6 and C7 then brings in C8 and C9 to form pore

  • form prepore complex whcih inserts itno the target cell membrane
  • mutliple C8, C9 proteins attach to form membrane attack complex (MAC) pore complex

*result - lysis of target cell

34
Q

C3b is a potent ___

A

opsonin

  • opsonins promote phagocytosis of the opsonized roganism

*bind to antibodies adn to receptors on macrophage

35
Q

C3a and C5a are _______

A

anaphylatoxins (inducers of inflammation)

  • activate other innate cells

MICR 2420 (29 decks)

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